Ontogeny of cyclooxygenase-1 and cyclooxygenase-2 gene expression in ovine lung.
Prostacyclin is a key mediator of pulmonary vascular and parenchymal function during late fetal and early postnatal life, and its synthesis in whole lung increases during that period. The rate-limiting enzyme in prostacyclin synthesis in the developing lung is cyclooxygenase (COX). We investigated the ontogeny and cellular localization of COX-1 (constitutive) and COX-2 (inducible) gene expression in lungs from late-gestation fetal lambs, 1-wk-old newborn lambs (NB1), and 1- to 4-mo-old newborn lambs (NB2). COX-1 mRNA abundance rose progressively from fetal to NB1 to NB2, increasing 12-fold overall. In parallel, immunoblot analysis revealed a progressive increase in COX-1 protein, rising fourfold from fetal lambs to NB2. COX-2 mRNA levels increased fivefold from fetal to NB1 but were similar in NB1 and NB2. However, COX-2 protein was not detectable by immunoblot analysis in any age group. Immunohistochemistry for COX-1 showed intense immunostaining in endothelial cells at all ages. COX-1 was also expressed in airway epithelium at all ages, with a greater number of epithelial cells staining positively in NB2 compared with fetal and NB1 groups. In addition, COX-1 was expressed in airway smooth muscle from NB1. COX-2 immunostaining was absent in all age groups. These findings indicate that there is differential expression of COX-1 and COX-2 in the developing lung and that the enzymes are expressed in a cell-specific manner. The developmental upregulation in COX-1 may optimize the capacity for prostaglandin-mediated vasodilation, bronchodilation, and surfactant synthesis in the newborn lung.
Brannon
T S
TS
Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas 75235-9063, USA.
MacRitchie
A N
AN
Jaramillo
M A
MA
Sherman
T S
TS
Yuhanna
I S
IS
Margraf
L R
LR
Shaul
P W
PW
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D004730:Endothelium, Vascular / Q000201:enzymology; D004847:Epithelial Cells / Q000201:enzymology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D005865:Gestational Age; D007527:Isoenzymes / Q000096:biosynthesis*; D008168:Lung / Q000196:embryology / Q000201:enzymology* / Q000254:growth & development; D009130:Muscle, Smooth / Q000201:enzymology; D009131:Muscle, Smooth, Vascular / Q000201:enzymology; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D011652:Pulmonary Circulation; D012333:RNA, Messenger / Q000096:biosynthesis; D012756:Sheep; D014158:Transcription, Genetic
D007527:Isoenzymes; D012333:RNA, Messenger; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases